Increasing evidence that diol epoxides are important intermediates in the mutagenesis and carcinogenesis of polycyclic aromatic hydrocarbons has been amassed during the past year. Quantum chemical calculations which we applied to estimate the reactivity of diol epoxides have proven successful in correctly predicting that bay region epoxides should be the most reactive for a given PAH, and have correctly predicted the relative reactivity of diol epoxides derived from different PAH. PAH ring-substituted with nitrogen (aza-PAH) are being increasingly recognized as significant environmental contaminants, but have received meager attention from the standpoint of determining the metabolites involved in the carcinogenesis of the compounds and their structure-activity relationships. An examination of the literature on benz(c)acridine derivatives suggests that diol epoxide and dihydrodiol intermediates analogous to those involved in PAH carcinogenesis may well be involved. The dihydrodiol and diol epoxide derivatives of benz(c)acridine will be synthesized in the author's laboratory and will be tested for biological activity through the collaboration of D.M. Jerina, Laboratory of Bio-organic Chemistry, NIAMDD and A.H. Conney at Hoffmann-LaRoche. The biological testing will entail studies of the ability of the dihdrodiols to be metabolically activated by a cytochrome P-450 enzyme system to species mutagenic to mutant Salmonella strains as well as examination of the intrinsic mutagenicity of the diol epoxide and other derivatives of benz(c)acridine. Selected derivatives will be examined for carcinogenicity depending upon the mutagenicity results. The dihydrodiols and diol epoxides will be made available for metabolism studies. Additionally, dimethyl derivatives of benzo(a)pyrene will be synthesized to probe the importance of steric effects in the enzymatic epoxidation of double bonds in benzo rings of PAH and in the hydration of benzo ring tetrahydroepoxides with epoxide hydrase. A new stereospecific synthesis has been designed to make available benzo ring diol epoxides that are very difficult to prepare by current methods and will be pursued.